We propose to study the metabolic effects of the interaction between plasma glycosaminoglycans (GAG) and low density lipoproteins (LDL). The binding of LDL to specific receptors on the cell surface is the first step in the sequence of events leading to its intracellular degradation. It is conceivable that formation of GAG-LDL complexes in the extracellulr space might interfere with or modify the binding of LDL to its receptors, thus affecting its intracellular translocation and degradation. Two different methodologies will be employed to verify this hypothesis: 1) the binding of (125I)LDL to cultured skin fibroblasts, in presence and absence of purified plasma GAG; 2) the agglutination of LDL-coated formocells by isolated LDL receptors, in presence and absence of purified plasma GAG. Plasma GAG have been separated into two different types on the basis of molecular weight and degree of sulfation. Our recent experiments have demonstrated that those of high molecular weight and sulfate content agglutinate LDL-coated formocells, while those of low molecular weight and sulfate content do not. However, the latter ones also bind LDL-coated formocells, since in proper proportions they prevent their agglutination. Therefore, we will evaluate whether different proportions of the two types of plasma GAG may modulate the binding of LDL to isolated receptors or their metabolism by cultured fibrobasts. Such findings might elucidate the role of extracellular GAG in the regulation of LDL metabolism and cholesterol synthesis. Since the high molecular weight plasma GAG are the products of partial degradation of tissue proteoglycans, we propose to investigate how their further degradation or desulfation might affect the binding of LDL to its specific receptors.